Kinetics of induction and growth of precancerous liver-cell foci, and liver tumour formation by diethylnitrosamine in the rat. |
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| Authors: | E Scherer P Emmelot |
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| Affiliation: | 1. Innovation Research Institute of traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China;2. State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, 276006, China;3. Shandong University of Traditional Chinese Medicine, 4655 University Road, Jinan, 250355, China;1. Regulation of Iron Metabolism Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy;2. Vita-Salute San Raffaele University, Milan, Italy;3. Gene Transfer into Stem Cell Unit, SR-Tiget, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy;4. Ionis Pharmaceuticals Inc., Carlsbad, California, USA;1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China;2. Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China;1. The State Key Laboratory of Medicinal Chemical Biology & College of Chemistry, Nankai University, Tianjin, 300071, China;2. College of Pharmacy, Nankai University, Tianjin, 300071, China;3. State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, 276005, China;1. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China;2. State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 276005, China;3. Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Lunan Pharmaceutical Group Co. LTD., Linyi, 273400, China;4. College of Traditional Chinese Medicine, Beijing University of Traditional Chinese Medicine, Beijing, 100029, China;5. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China;6. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China;1. Austrian Center for Medical Innovation and Technology, Wiener Neustadt, Austria;2. Research Center for Medical Image Analysis and Artificial Intelligence (MIAAI), Department of Medicine, Danube Private University, Krems, Austria;3. Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria;4. Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria;5. Institute of Diagnostic, Interventional Radiology and Nuclear Medicine, Landesklinikum Wiener Neustadt, Wiener Neustadt, Austria;6. Department of Radiology and Nuclear Medicine, Medical University Vienna, Austria |
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| Abstract: | Induction of foci of atypical liver cells (ATPase-deficient islands, which previously have been shown to serve as tumour cell precursor) by a single dose of diethyl-nitrosamine in partially hepatectomized rats showed direct proportionality between number of islands and dose up to 30 mg DENA/kg, pointing to a one-hit mechanism of induction. The curve relating number of islands to dose levelled off at ≧ 50 mg/kg, and this was interpreted as resulting mainly from the toxic action of the carcinogen. Island size (the number of cells per island) was independent of dose up to 30 mg DENA/kg, but progressively increased in the higher dose range. Increased proliferation of island cells was attributed to the regenerative stimulus stemming from the toxic effect of the carcinogen at the higher doses. Analogous findings resulted from the measurement of island induction in the livers of intact rats receiving 0·9–14 mg DENA/kg daily for 4 weeks.A single dose of ≧ 50 mg DENA/kg produced hepatocellular tumours in the partially hepatectomized rat. Liver tumour formation in this system is discussed and the significance of cell proliferation (DNA synthesis) for the various phases of the hepatocarcinogenic process is stressed. |
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